This project is just completing its ninth year of MN funding. Originally we suggested that certain skeletal muscles could be made fatigue resistant by electrical stimulation and then fashioned into pumps and used to pump fluid in a mock circulation device. We accomplished this early on and showed with in-circulation experiments the muscle pumps generated stroke work between that of the right and left ventricle. These skeletal muscle ventricles (SMVs) pumped blood effectively in the circulation for many weeks before the animals died of thromboembolic complications. In the second three-year and current three-year funding periods, we tested numerous types of SMVs of different designs, with mock circulation devices and in circulation. We progressively improved pump function, decreased thromboembolic and other complications, while increasing pump endurance to where an SMV pumped blood effectively in the circulation for 836 days. To our knowledge this is the longest surviving laboratory animal or human with a functioning heart assist. This 3-year grant proposal is different; it now focusses towards one endpoint; to develop at least one and possibly two clinically applicable SMV left heart assist models. The proposed research is based on successful SMV models already developed during this funding period, which need more refinement and testing. In our SMV aortic counterpulsator, the thoracic aorta is ligated to cause obligatory blood flow through the SMV. Clearly, ligating the aorta in a clinical situation is not ideal. Therefore we propose to modify the SMV aortic counterpulsator to eliminate the necessity for ligation of the aorta. Secondly, the SMV left ventricular apex to aortic configuration is the most hemodynamically effective skeletal muscle cardiac assist device that we have tested. However, from the Progress Report (Experiments 15 and 16), refinement is needed before this system can be used clinically. This 3-year plan allows for SMV refinement and should set the stage for clinical use.